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Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
Neural checkpoint therapy in lung cancer
Glori Das1, Hong Zhao2, Stephen T C Wong3
1T. T. and W. F. Chao Center for BRAIN, Houston Methodist Neal Cancer Center, Houston Methodist, Houston, TX 77030, USA; Texas A&M University College of Medicine, Bryan, TX 77807, USA.
Trends in Cancer
|July 13, 2026
Summary
Sensory nerves regulate tumor immunity. A novel neuron-calcitonin gene-related peptide pathway in lung cancer impairs immune responses, indicating neural checkpoint blockade could enhance immunotherapy effectiveness.
Area of Science:
- Oncology
- Neuroscience
- Immunology
Background:
- Sensory nerves are increasingly recognized as key regulators of the tumor microenvironment and immune responses.
- Lung adenocarcinoma (LUAD) often exhibits an "immune-cold" phenotype, characterized by limited immune cell infiltration and poor response to immunotherapy.
- Understanding the interplay between neural signaling and anti-tumor immunity is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of a specific sensory nerve pathway involving Nav1.8+ neurons and calcitonin gene-related peptide (CGRP) in LUAD.
- To elucidate how this neural axis influences tertiary lymphoid structure (TLS) formation and anti-tumor immunity in LUAD.
- To explore the potential of targeting this neural axis for enhancing immunotherapy efficacy in LUAD.
Main Methods:
- Utilized a combination of immunohistochemistry and molecular analyses to identify and characterize Nav1.8+ neurons and CGRP expression in LUAD tissues.
- Assessed the correlation between Nav1.8+/CGRP signaling and the presence/organization of TLS within the tumor microenvironment.
- Investigated the functional impact of this neural axis on immune cell infiltration and function using preclinical LUAD models.
Main Results:
- Identified a distinct Nav1.8+ neuron-CGRP signaling axis within the tumor microenvironment of LUAD.
- Demonstrated that this neural axis is associated with impaired TLS formation, leading to reduced immune cell infiltration.
- Showcased that blockade of this neural pathway can promote immune cell infiltration and remodel the immune-cold tumor microenvironment.
Conclusions:
- The Nav1.8+ neuron-CGRP axis represents a novel mechanism by which sensory nerves suppress anti-tumor immunity in LUAD.
- Targeting this neural pathway, potentially through neural checkpoint blockade, offers a promising strategy to enhance immunotherapy responses in immune-cold tumors.
- Further research into neuro-immune interactions in cancer holds significant potential for advancing oncological therapies.
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